Heparin in Medical Devices and Combination Products: Testing, Labeling and Safety Requirements
This guidance provides recommendations for medical devices and combination products containing heparin sodium or low molecular weight heparin that have a device primary mode of action (PMOA) or are regulated by CDRH. It covers both in vitro diagnostic devices containing heparin and combination products for in vivo use. Products with bonded heparin coatings may not need to follow all recommendations unless significant heparin release is observed.
Recommended Actions
- Review and update product labeling to ensure compliance with new strength expression requirements
- Implement testing protocols for OSCS detection
- Document heparin source and manufacturer information
- Establish procedures for handling contaminated materials
- Maintain comprehensive safety testing records
- Update quality system documentation to include heparin-specific controls
- Prepare documentation package for premarket submissions
- Implement monitoring system for heparin API quality
- Establish procedures for investigating and documenting deviations
- Review and update Instructions for Use to include required heparin information
Key Considerations
Non-clinical testing
- Testing for OSCS using qualified methods (e.g., strong anion exchange HPLC and 1H NMR)
- Testing according to current USP drug substance monograph
- Compliance with contaminant safety testing recommendations in USP monograph on Heparin Sodium
Labelling
- For Heparin Lock Flush Solution:
- Express strength per total container volume as primary expression
- Include strength per mL in parentheses
- Identify organ and animal species source
- For Heparin-Bonded Products:
- Generally no specific labeling needed for amount/strength
- May need total amount per surface area if significant leaching occurs
- Identify tissue and animal species source
Safety
- Must comply with Quality System regulation (21 CFR 820)
- For combination products: comply with both QS regulation and cGMP requirements
- Maintain documentation of heparin safety testing
- Implement procedures for handling contaminated materials
Other considerations
- Identify heparin source tissue and species origin
- Provide manufacturer information for heparin API
- Document compliance with testing parameters from guidance on crude heparin monitoring
Relevant Guidances
- Current Good Manufacturing Practice Requirements for Combination Products
- Compliance Policy for Combination Product Postmarketing Safety Reporting Requirements
- Premarket Review Pathways for Combination Products
- User Fees for Combination Products and Associated Waivers
- Postmarketing Safety Reporting Requirements for Combination Products
Related references and norms
- USP <7>: Labeling
- ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Original guidance
- Heparin in Medical Devices and Combination Products: Testing, Labeling and Safety Requirements
- HTML / PDF
- Issue date: 2018-09-20
- Last changed date: 2019-04-12
- Status: FINAL
- Official FDA topics: Medical Devices, Premarket Approval (PMA), Drugs, 510(k), Premarket, Combination Products, HUD/HDE
- ReguVirta summary file ID: ca4d4fde09c5465f06d86059147b2411
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